This is an application to renew a clinical trials unit (CTU) in Botswana, which has the second-highest prevalence of HIV in the world but also a sympathetic and interested government. This program will engage in research related to adult HIV therapeutic strategies (including antiretroviral treatment strategies, the diagnosis/management of noninfectious co-morbidities, and the infectious co-morbidities of hepatitis and tuberculosis); strategies to address HIV and HIV-associated infections/conditions in piediatric and maternal populations; integrated HIV prevention strategies in pediatric and adult populations; and vaccines to prevent HIV infection. These activities will occur through participation in four networks: ACTG, IMPAACT, HPTN, and HVTN. The objectives are to help develop and facilitate strategies for prevention and treatment of HIV infection and HIV-related illnesses (and for HIV vaccines) that are relevant for alleviating the epidemic in sub-Saharan Africa and elsewhere. Investigators and other key personnel from the Botswana CTU will participate in and contribute to network scientific and leadership activities in all areas, including joining and potentially leading protocol teams and scientific / resource committees ofthe networks with which this CTU will be affiliated. The Botswana CTU will conduct an integrated program for clinical research that includes clinical and laboratory activities. Two established clinical research sites (in Gaborone and Molepolole) will be affiliated with this CTU, and will allow efficient enrollment of participants in both urban and village populations into trials in Botswana. The investigators and staff are highly experienced in AIDS research, including trials in all proposed research areas, and have a strong record of collaboration with national and international agencies and networks, and a substantial record of having completed trials with very high standards. The combined resources of the Botswana CTU are substantial for both facilities and personnel.